中文摘要：

基于＂底物包膜＂假说,以现有HIV-1蛋白酶抑制剂Darunavir为模板构建药效团模型并对中药化学数据库进行搜索;采用分子对接方法进一步考察化合物与HIV-1蛋白酶结合情况及其与＂底物包膜＂符合程度,优先选出两个化合物Annomonicin和去乙酰蟾蜍它灵;应用分子动力学方法对这两个化合物进行动力学模拟,观察它们与蛋白酶结合的复合物在动力学过程中的稳定性并计算其结合自由能,综合评价筛选结果,最终确定化合物Annomonicin具有更潜在的深入研究价值.

英文摘要：

Based on the Substrate Envelope Hypothesis and the available HIV-1 protease inhibitor darunavir, a new pharmacophore model of HIV-1 protease inhibitors was constructed, and applied to the Traditional Chinese Medicine Database searching. By molecular docking, two compounds of novel structure that not only bind well with the HIV-1 protease, but also fit well within the substrate envelope, were found. They were annomonicin and desacetylbufotalin. Then molecular dynamics simulations were used to study these two compounds, which were complexed with HIV-1 protease in explicit water molecules. The structural stability and binding free energies were selected to evaluate these two compounds. With the hybrid method taking advantage of the synergistic effects of structure-based and ligand-based drug design techniques, the two new compounds were selected as the candidate compounds in this work. Through theory study and analysis, annomonicin is worthy of further study and research.